Preferred genetic test for the detection of variants causing X-linked Alport syndrome.
Polymerase Chain Reaction/ Sequencing/Multiplex Ligation-dependent Probe Amplification
Lavender (EDTA), pink (K2EDTA), or yellow (ACD solution A or B).
Transport 3 mL whole blood. (Min: 2 mL)
Ambient: 72 hours; Refrigerated: 1 week; Frozen: Unacceptable
Background Information for: Alport Syndrome, X-linked (COL4A5) Sequencing and Deletion/Duplication
Characteristics: Progressive renal and cochlear disease with 30-40 percent incidence of ocular involvement; 60 percent of males reach end-stage renal disease by age 30, and 85 percent have sensorineural deafness by age 40.
Incidence: Approximately 1 in 50,000 live births.
Inheritance: X-linked recessive; de novo mutations in 10-15 percent of affected males.
Penetrance: Variable, depending on mutation and sex.
Cause: Pathogenic type 4 collagen alpha chain 5 (COL4A5) mutations.
Clinical Sensitivity: Greater than 80 percent for X-linked Alport syndrome in males or females.
Methodology: Bidirectional sequencing of the entire COL4A5 coding region and intron-exon boundaries and multiplex ligation-dependent probe amplification (MLPA) to detect large COL4A5 coding region deletions and duplications.
Analytical Sensitivity & Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations. Regulatory region mutations and deep intronic mutations will not be detected. Breakpoints of deletions/duplications will not be determined. Mutations in genes, other than COL4A5, are not evaluated. Deletions/duplications in exons 8, 25, 40, 42, and 43 of the COL4A5 gene will not be detected.
Laboratory Developed Test (LDT)
|Component Test Code*||Component Chart Name||LOINC|
|2002399||ALPORT FGA Specimen||31208-2|
|2002401||Alport (COL4A5) Seq and Del/Dup Interp||53853-8|
- Alport syndrome molecular testing
- X-linked Alport syndrome molecular testing